We propose to continue our studies of the physiology of exocrine glands, and of the pathogenesis and exocrine gland dysfunction of cystic fibrosis. The cellular physiological, pharmacological and biochemical aspects of secretion will be studied in vitro using enzymatically dispersed morphologically and functionally intact rat parotid acinar cells. Cell preservation under cell culture conditions will be attempted. The same cellular mechanisms of secretion will be studied in human parotid acinar cells derived through enzymatic dispersion of human parotids obtained either at surgery or immediately after death and in cells from other exocrine glands such as the pancreas. The cellular studies will be complemented by parallel studies of exocrine gland function using either conventional methodologies or micropuncture and microperfusion techniques. In cystic fibrosis, we plan to investigate the cellular pathophysiology of isolated acinar cells obtained from parotids of patients immediately after death. We also plan to study the role of a possible defect of polyamine metabolism in homozygotes and heterozygotes for cystic fibrosis and its role in the pathogenesis of the membrane dysfunction of cystic fibrosis.